全文获取类型
收费全文 | 2034篇 |
免费 | 165篇 |
国内免费 | 1篇 |
专业分类
电工技术 | 10篇 |
综合类 | 1篇 |
化学工业 | 767篇 |
金属工艺 | 22篇 |
机械仪表 | 54篇 |
建筑科学 | 70篇 |
矿业工程 | 1篇 |
能源动力 | 52篇 |
轻工业 | 398篇 |
水利工程 | 14篇 |
石油天然气 | 6篇 |
无线电 | 122篇 |
一般工业技术 | 288篇 |
冶金工业 | 158篇 |
原子能技术 | 12篇 |
自动化技术 | 225篇 |
出版年
2024年 | 1篇 |
2023年 | 24篇 |
2022年 | 150篇 |
2021年 | 235篇 |
2020年 | 99篇 |
2019年 | 77篇 |
2018年 | 86篇 |
2017年 | 68篇 |
2016年 | 86篇 |
2015年 | 73篇 |
2014年 | 98篇 |
2013年 | 130篇 |
2012年 | 115篇 |
2011年 | 141篇 |
2010年 | 110篇 |
2009年 | 87篇 |
2008年 | 85篇 |
2007年 | 77篇 |
2006年 | 59篇 |
2005年 | 56篇 |
2004年 | 40篇 |
2003年 | 26篇 |
2002年 | 41篇 |
2001年 | 20篇 |
2000年 | 16篇 |
1999年 | 18篇 |
1998年 | 45篇 |
1997年 | 30篇 |
1996年 | 22篇 |
1995年 | 18篇 |
1994年 | 7篇 |
1993年 | 8篇 |
1992年 | 3篇 |
1991年 | 3篇 |
1990年 | 5篇 |
1989年 | 7篇 |
1988年 | 4篇 |
1987年 | 1篇 |
1986年 | 1篇 |
1983年 | 2篇 |
1982年 | 4篇 |
1981年 | 2篇 |
1980年 | 1篇 |
1979年 | 2篇 |
1976年 | 12篇 |
1973年 | 1篇 |
1972年 | 1篇 |
1969年 | 2篇 |
1966年 | 1篇 |
排序方式: 共有2200条查询结果,搜索用时 453 毫秒
101.
Dr. Markella Konstantinidou Francesca Magari Fandi Sutanto Dr. Jörg Haupenthal Dr. Varsha R. Jumde Dr. M. Yagiz Ünver Prof. Dr. Andreas Heine Dr. Carlos Jamie Camacho Prof. Dr. Anna K. H. Hirsch Prof. Dr. Gerhard Klebe Prof. Dr. Alexander Dömling 《ChemMedChem》2020,15(8):680-684
Pharmacophore searches that include anchors, fragments contributing above average to receptor binding, combined with one-step syntheses are a powerful approach for the fast discovery of novel bioactive molecules. Here, we are presenting a pipeline for the rapid and efficient discovery of aspartyl protease inhibitors. First, we hypothesized that hydrazine could be a multi-valent warhead to interact with the active site Asp carboxylic acids. We incorporated the hydrazine anchor in a multicomponent reaction and created a large virtual library of hydrazine derivatives synthetically accessible in one-step. Next, we performed anchor-based pharmacophore screening of the libraries and resynthesized top-ranked compounds. The inhibitory potency of the molecules was finally assessed by an enzyme activity assay and the binding mode confirmed by several soaked crystal structures supporting the validity of the hypothesis and approach. The herein reported pipeline of tools will be of general value for the rapid generation of receptor binders beyond Asp proteases. 相似文献
102.
Davide Ciardiello Brigida Anna Maiorano Paola Parente Maria Grazia Rodriquenz Tiziana Pia Latiano Cinzia Chiarazzo Valerio Pazienza Luigi Pio Guerrera Brunella Amoruso Nicola Normanno Giulia Martini Fortunato Ciardiello Erika Martinelli Evaristo Maiello 《International journal of molecular sciences》2022,23(2)
Biliary tract cancers (BTC) represent a heterogeneous and aggressive group of tumors with dismal prognosis. For a long time, BTC has been considered an orphan disease with very limited therapeutic options. In recent years a better understanding of the complex molecular landscape of biology is rapidly changing the therapeutic armamentarium. However, while 40–50% of patients there are molecular drivers susceptible to target therapy, for the remaining population new therapeutic options represent an unsatisfied clinical need. The role of immunotherapy in the continuum of treatment of patients with BTC is still debated. Despite initial signs of antitumor-activity, single-agent immune checkpoint inhibitors (ICIs) demonstrated limited efficacy in an unselected population. Therefore, identifying the best partner to combine ICIs and predictive biomarkers represents a key challenge to optimize the efficacy of immunotherapy. This review provides a critical analysis of completed trials, with an eye on future perspectives and possible biomarkers of response. 相似文献
103.
Alice Albergamo Giulia Apprato Francesca Silvagno 《International journal of molecular sciences》2022,23(7)
The genomic activity of vitamin D is associated with metabolic effects, and the hormone has a strong impact on several physiological functions and, therefore, on health. Among its renowned functions, vitamin D is an immunomodulator and a molecule with an anti-inflammatory effect, and, recently, it has been much studied in relation to its response against viral infections, especially against COVID-19. This review aims to take stock of the correlation studies between vitamin D deficiency and increased risks of severe COVID-19 disease and, similarly, between vitamin D deficiency and acute respiratory distress syndrome. Based on this evidence, supplementation with vitamin D has been tested in clinical trials, and the results are discussed. Finally, this study includes a biochemical analysis on the effects of vitamin D in the body’s defense mechanisms against viral infection. In particular, the antioxidant and anti-inflammatory functions are considered in relation to energy metabolism, and the potential, beneficial effect of vitamin D in COVID-19 is described, with discussion of its influence on different biochemical pathways. The proposed, broader view of vitamin D activity could support a better-integrated approach in supplementation strategies against severe COVID-19, which could be valuable in a near future of living with an infection becoming endemic. 相似文献
104.
Some hearing, vestibular, and vision disorders are imputable to voltage-gated Ca2+ channels of the sensory cells. These channels convey a large Ca2+ influx despite extracellular Na+ being 70-fold more concentrated than Ca2+; such high selectivity is lost in low Ca2+, and Na+ can permeate. Since the permeation properties and molecular identity of sensory Ca2+ channels are debated, in this paper, we examine the Na+ current flowing through the L- and R-type Ca2+ channels of labyrinth hair cells. Ion currents and cytosolic free Ca2+ concentrations were simultaneously monitored in whole-cell recording synchronous to fast fluorescence imaging. L-type and R-type channels were present with different densities at selected sites. In 10 nM Ca2+, the activation and deactivation time constants of the L-type Na+ current were accelerated and its maximal amplitude increased by 6-fold compared to physiological Ca2+. The deactivation of the R-type Na+ current was not accelerated, and its current amplitude increased by 2.3-fold in low Ca2+; moreover, it was partially blocked by nifedipine in a voltage- and time-dependent manner. In conclusion, L channel gating is affected by the ion species permeating the channel, and its selectivity filter binds Ca2+ more strongly than that of R channel; furthermore, external Ca2+ prevents nifedipine from perturbing the R selectivity filter. 相似文献
105.
106.
Pianetti A Manti A Boi P Citterio B Sabatini L Papa S Rocchi MB Bruscolini F 《International journal of food microbiology》2008,127(3):252-260
Aeromonads in waters and foods can represent a risk to human health. Factors such as sodium chloride concentration and temperature can affect growth and viability of several food and water-borne pathogens. The behaviour of an Aeromonas hydrophila strain in the presence of 1.7%, 3.4% and 6% NaCl concentrations at 24 degrees C and 4 degrees C was studied over a 188 day period. Viability and membrane potential were assessed by flow cytometry; growth was evaluated by plate count technique. Flow cytometry evidenced that A. hydrophila retained viability over the period although varying according to temperature and salt concentrations. Colony Forming Units were generally lower in number than viable cells especially in the presence of 6% NaCl, indicating the occurrence of stressed cells which maintain metabolic activity yet are not able to grow on agar plates. In conclusion, A. hydrophila showed a long-term halotolerance even at elevated (6%) NaCl concentrations and a lesser sensitivity to salt at low temperature; therefore, low temperature and salt, which are two important factors limiting bacterial growth, do not assure safety in the case of high initial contamination. Finally, cytometry appears a valid tool for the rapid detection of the viability of pathogenic bacteria in food and environmental matrices to control and prevent health risks. 相似文献
107.
Francesca Antonucci Federico Pallottino Graziella Paglia Amedeo Palma Salvatore D��Aquino Paolo Menesatti 《Food and Bioprocess Technology》2011,4(5):809-813
Sugar content is one of the most important quality attributes of citrus fruit, either for fresh or for processing market.
Since sugars in citrus juice are highly correlated with total soluble solids (TSS) content, which can be determined easily
even by the means of a hand refractometer, TSS is one of the most frequently used quality index. Since TSS can be measured
only destructively, the results are representative only if carried out on large samples and do not allow classifying marketable
fruit one by one according to their specific sugar content. Objective of this experiment was to assess possibility and limits
of a non-destructive estimation of citrus fruits internal quality parameters (TSS and titratable acidity) presenting thick
peel by the use of a spectrophotometric portable VIS-NIR system. Four hundred fruit of “Miho” satsuma and 150 fruit of “Page”
tangelo were used. Each fruit was first subjected to spectrophotometric acquisition and soon after was juiced and TSS and
titratable acidity (TA) determined. Partial least squares (PLS) regression analysis was applied for constructing a predictive
model based on the spectral normalized response, constructing the model on a sub-sample and verifying the model (prediction
test) on independent ones. The TA relative to Page mandarin was predicted in the test with an r = 0.88 and a standard error of prevision (SEP) coefficient of variability of 3.8% while the TSS scored an r = 0.85 and a SEP coefficient of variability equal to 4%. The TA of Miho mandarin was predicted in the test with an r = 0.81 and a SEP coefficient of Variability of 8.3% while the TSS scored an r = 0.84 and a SEP coefficient of variability equal to 5.6%. 相似文献
108.
Plewa MJ Muellner MG Richardson SD Fasano F Buettner KM Woo YT McKague AB Wagner ED 《Environmental science & technology》2008,42(3):955-961
The haloacetamides, a class of emerging nitrogenous drinking water disinfection byproduct (DBPs), were analyzed for their chronic cytotoxicity and for the induction of genomic DNA damage in Chinese hamster ovary cells. The rank order for cytotoxicity of 13 haloacetamides was DIAcAm > IAcAm > BAcAm > TBAcAm > BIAcAm > DBCAcAm > CIAcAm > BDCAcAm > DBAcAm > BCAcAm > CAcAm > DCAcAm > TCAcAm. The rank order of their genotoxicity was TBAcAm > DIAcAm approximately equal to IAcAm > BAcAm > DBCAcAm > BIAcAm > BDCAcAm > CIAcAm > BCAcAm > DBAcAm > CAcAm > TCAcAm. DCAcAm was not genotoxic. Cytotoxicity and genotoxicity were primarily determined by the leaving tendency of the halogens and followed the order I > Br > > Cl. With the exception of brominated trihaloacetamides, most of the toxicity rank order was consistent with structure-activity relationship expectations. For di- and trihaloacetamides, the presence of at least one good leaving halogen group (I or Br but not Cl) appears to be critical for significant toxic activity. Log P was not a factor for monohaloacetamides but may play a role in the genotoxicity of trihaloacetamides and possible activation of dihaloacetamides by intracellular GSH and -SH compounds. 相似文献
109.
Anay Priscilla David de Oliveira Mateus Matiuzzi da Costa Daniel Maia Nogueira Francesca Silva Dias 《International Journal of Dairy Technology》2020,73(2):345-356
Twenty isolates from milk and goat cheese were confirmed as Staphylococcus aureus. These isolates were characterised for phenotypic properties related to cell adhesion and for the presence of enterotoxin production, intercellular adhesion and β‐lactam resistance genes. Staphylococcus aureus L47 showed cell adhesion ability and positivity for the sec, sed, icaD, mecA and blaZ genes. Three antimicrobial compounds were tested singly or in pairs for growth control of strain L47: gallic acid (GA), nisin and essential oil (EO) of Croton heliotropiifolius (velame). At 24 h, EO and EO + nisin showed higher inhibitory activity against S. aureus L47 in goat milk. 相似文献
110.
Francesca M. Piras Eleonora Cappelletti Marco Santagostino Solomon G. Nergadze Elena Giulotto Elena Raimondi 《International journal of molecular sciences》2022,23(8)
The centromere is the chromosomal locus essential for proper chromosome segregation. While the centromeric function is well conserved and epigenetically specified, centromeric DNA sequences are typically composed of satellite DNA and represent the most rapidly evolving sequences in eukaryotic genomes. The presence of satellite sequences at centromeres hampered the comprehensive molecular analysis of these enigmatic loci. The discovery of functional centromeres completely devoid of satellite repetitions and fixed in some animal and plant species represented a turning point in centromere biology, definitively proving the epigenetic nature of the centromere. The first satellite-free centromere, fixed in a vertebrate species, was discovered in the horse. Later, an extraordinary number of satellite-free neocentromeres had been discovered in other species of the genus Equus, which remains the only mammalian genus with numerous satellite-free centromeres described thus far. These neocentromeres arose recently during evolution and are caught in a stage of incomplete maturation. Their presence made the equids a unique model for investigating, at molecular level, the minimal requirements for centromere seeding and evolution. This model system provided new insights on how centromeres are established and transmitted to the progeny and on the role of satellite DNA in different aspects of centromere biology. 相似文献